We propose to study the fine structural changes in the spinal cord and roots, as well as peripheral nerves and skeletal muscle of a mutant hamster which shows hind leg paralysis. Relatively young mutants, up to nine months of age, have already been studied and previously unknown morphological changes have been observed in the Schwann cells of the peripheral nerves and roots. These include enormous accumulations of filaments, associated crystalloid formations in the inner loops of Schwann cells, and subsequent demyelination and remyelination. Axonal changes, including filament accumulations were also present. Our plan is to investigate (1) the relationship between the axonal and Schwann cell changes, (2) the origin of the filaments and the crystalloid formatin, the so-called Hirano body, (3) the connection between these changes and demyelination, (4) whether or not onion bulb formation eventually occurs, and (5) the changes in the anterior horn cells, if any, in the chronic stages of the disease and its relevance to familial Amyotrophic Lateral Sclerosis (ALS).